Korean Journal of Nephrology 2009;28(2):103-112.
Erythropoietin (EPO) Attenuates Renal Injury in an Experimental Model of Cisplatin-induced Nephrotoxicity in Rats
Dae Eun Choi, M.D.1, Sarah Chung, M.D.1, Young Mo Lee, M.D., Ph.D.2, Kwang-Sun Suh, M.D., Ph.D.3, Ki-Ryang Na, M.D., Ph.D.1, Young-Tai Shin, M.D., Ph.D.1 and Kang Wook Lee, M.D., Ph.D.1
Department of Internal Medicine1
Chungnam National University Hospital, Chungnam Department of Internal Medicine2
Korea University Guro Hospital, Seoul Department of Pathology3
Chungnam National University Hospital, Chungnam, Korea
기초연구 : Erythropoietin (EPO) Attenuates Renal Injury in an Experimental Model of Cisplatin-induced Nephrotoxicity in Rats
Dae Eun Choi, M.D.1, Sarah Chung, M.D.1, Young Mo Lee, M.D., Ph.D.2, Kwang-Sun Suh, M.D., Ph.D.3, Ki-Ryang Na, M.D., Ph.D.1, Young-Tai Shin, M.D., Ph.D.1 and Kang Wook Lee, M.D., Ph.D.1
Department of Internal Medicine1, Chungnam National University Hospital, Chungnam Department of Internal Medicine2, Korea University Guro Hospital, Seoul Department of Pathology3, Chungnam National University Hospital, Chungnam, Korea
Abstract
Purpose:In addition to its hematopoietic effects, EPO has protective effects in vivo in several animal models of acute renal injury. We examined whether EPO also attenuated renal injury in a rat model of cisplatin-induced nephrotoxicity via anti-apoptotic and anti-inflammatory actions. Methods:Male SpragueDawley rats were divided into four groups: control rats, EPO+control rats, cisplatin rats, and EPO+cisplatin rats. EPO treatment was started 24 h prior to cisplatin administration. Then, 96 h after cisplatin administration, all experimental animals were killed. And renal molecular, functional and structural parameters were measured. Results:The serum levels of BUN and creatinine in the 96 h after cisplatin administration were significantly lower than in cisplatin rats. On microscopic examination, the magnitude of renal tubular epithelial damage in the EPO+cisplatin rats was also significantly less than that of cisplatin rats. Renal expression of TNF-α, Fas, MCP-1 and TGF-β in the cisplatin rats was significantly higher than those of control rats and EPO+control rats. The levels of TNF-α, Fas, MCP-1 and TGF-β gene expression in EPO+cisplatin rats were significantly lower than those of cisplatin rats. The Bcl-2 mRNA level in EPO+cisplatin rats was significantly higher than in cisplatin rats. EPO+cisplatin rats had significantly fewer TUNEL-positive cells. Conclusion:These results suggest that EPO has a protective effect against experimental cisplatin- induced renal injury and that the anti-inflammatory and anti-apoptotic properties of EPO may be involved.
Key Words: Apoptosis, Cisplatin, Erythropoietin, Inflammation
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